Hiv

Guidelines for the Use of Antiretroviral
Agents in HIV-1-Infected
Adults and Adolescents

December 1, 2009

Developed by the DHHS Panel on
Antiretroviral Guidelines for Adults
and Adolescents – A Working Group of the
Office of AIDS Research Advisory Council (OARAC)

How to Cite the Adult and Adolescent Guidelines:
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral
agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. December
1, 2009; 1-161. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Accessed (insert date) [insert page number, table number, etc. if applicable]

It is emphasized that concepts relevant to HIV management evolve
rapidly. The Panel has a mechanism to update recommendations on a
regular basis, and the most recent information is available on the
AIDSinfo Web site (http://aidsinfo.nih.gov).

December 1, 2009

What’s New in the Document?
The following key changes were made to update the November 3, 2008, version of the guidelines. Significant updates
are highlighted throughout the document.

New Section

Based on interests and requests from HIV practitioners, a new section entitled “Considerations in Managing
Patients with HIV-2 Infection” has been added to the guidelines. This new section briefly reviews the current
knowledge on the epidemiology and diagnosis of HIV-2 infection and the role of antiretroviral therapy in the
management of patients with HIV-2 mono-infection and HIV-1/HIV-2 coinfection.

Key Updates

Drug Resistance Testing
In this revision, the Panel provides more specific recommendations on when to use genotypic versus phenotypic
testing to guide therapy in treatment-experienced patients with viremia while on treatment.
• Genotypic testing is recommended as the preferred resistance testing to guide therapy in patients with
suboptimal virologic responses or virologic failure while on first or second regimens (AIII).
• Addition of phenotypic testing to genotypic testing is generally preferred for persons with known or suspected
complex drug resistance mutation patterns, particularly to protease inhibitors (BIII).

Initiation of Antiretroviral Therapy
In this updated version of the guidelines, the Panel recommends earlier initiation of antiretroviral therapy with the
following specific recommendations:
• Antiretroviral therapy should be initiated in all patients with a history of an AIDS-defining illness or with
CD4 count < 350 cells/mm3 (AI).
• Antiretroviral therapy should also be initiated, regardless of CD4 count, in patients with the following
conditions: pregnancy (AI), HIV-associated nephropathy (AII), and hepatitis B virus (HBV) coinfection when
treatment of HBV is indicated (AIII).
• Antiretroviral therapy is recommended for patients with CD4 counts between 350 and 500 cells/mm3. The
Panel was divided on the strength of this recommendation: 55% of Panel members for strong recommendation
(A) and 45% for moderate recommendation (B) (A/B-II).
• For patients with CD4 counts >500 cells/mm3, 50% of Panel members favor starting antiretroviral therapy
(B); the other 50% of members view treatment as optional (C) in this setting (B/C-III).

Patients initiating antiretroviral therapy should be willing and able to commit to lifelong treatment and should
understand the benefits and risks of therapy and the importance of adherence (AIII). Patients may choose to postpone
therapy, and providers may elect to defer therapy, based on clinical and/or psychosocial factors on a case-by-case
basis.

What to Start in Antiretroviral-Naïve Patients
• Increasing clinical trial data in the past few years have allowed for better distinction between the virologic
efficacy and safety of different combination regimens. Instead of providing recommendations for individual
antiretroviral components to use to make up a combination, the Panel now defines what regimens are
recommended in treatment-naïve patients.
• Regimens are classified as “Preferred,” “Alternative,” “Acceptable,” “Regimens that may be acceptable but
more definitive data are needed,” and “Regimens to be used with caution.”
• The following changes were made in the recommendations:
o “Raltegravir + tenofovir/emtricitabine” has been added as a “Preferred” regimen based on the results
of a Phase III randomized controlled trial (AI).
o Four regimens are now listed as “Preferred” regimens for treatment-naïve patients. They are:

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Page i

December 1, 2009

 efavirenz/tenofovir/emtricitabine;
 ritonavir-boosted atazanavir + tenofovir/emtricitabine;
 ritonavir-boosted darunavir + tenofovir/emtricitabine; and
 raltegravir + tenofovir/emtricitabine.
o Lopinavir/ritonavir-based regimens are now listed as “Alternative” (BI) instead of “Preferred”
regimens, except in pregnant women, where twice-daily lopinavir/ritonavir + zidovudine/lamivudine
remains a “Preferred” regimen (AI).

Additional Updates

The following sections and their relevant tables have been substantially updated:
• What Not to Use
• Management of Treatment-Experienced Patients
• Treatment Simplification
• Hepatitis C Coinfection
• Antiretroviral-Associated Adverse Effects
• Antiretroviral Drug Interactions
• Preventing Secondary Transmission of HIV

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December 1, 2009

Table of Contents
Guidelines Panel Roster ...................................................................................................... vi

INTRODUCTION ....................................................................................................................... 1
Guidelines Development Process ........................................................................... 1

BASELINE EVALUATION ............................................................................... 4

LABORATORY TESTING FOR INITIAL ASSESSMENT AND
MONITORING WHILE ON ANTIRETROVIRAL THERAPY .............................. 5
CD4+ T-Cell Count ........................................................................................................ 7
Plasma HIV RNA Testing ........................................................................................... 7
Drug Resistance Testing ............................................................................................. 9
HLA-B*5701 Screening ............................................................................................... 15
Coreceptor Tropism Assays ...................................................................................... 16

TREATMENT GOALS ............................................................................................................. 19
Strategies to Achieve Treatment Goals ................................................................ 19

INITIATING ANTIRETROVIRAL THERAPY IN
TREATMENT-NAÏVE PATIENTS ................................................................................... 22
Benefits of Antiretroviral Therapy ............................................................................ 23
Potential Limitations of Earlier Initiation of Therapy ........................................ 27
Summary ........................................................................................................................... 28
Recommendations ......................................................................................................... 29
The Need for Early Diagnosis of HIV ..................................................................... 31
Conclusion ........................................................................................................................ 31

WHAT TO START: INITIAL COMBINATION REGIMENS FOR THE
ANTIRETROVIRAL-NAÏVE PATIENT............................................................ 37
Considerations When Selecting a First Antiretroviral Regimen for
Treatment-Naïve Patients ..................................................................................... 37
NNRTI–Based Regimens (1 NNRTI + 2 NRTIs) ............................................... 41
PI-Based Regimens (Ritonavir-Boosted or Unboosted PI + 2 NRTIs) .... 43
INSTI-Based Regimen (INSTI + 2 NRTIs) ........................................................... 46
Dual-NRTI Options as Part of Initial Combination Therapy .......................... 46
All-NRTI Regimens ........................................................................................................ 49
Other Treatment Option Under Investigation:
Insufficient Data to Recommend ...................................................................... 50

WHAT NOT TO USE.......................................................................................... 60
Antiretroviral Regimens Not Recommended ......................................................... 60
Antiretroviral Components Not Recommended ................................................... 60

MANAGEMENT OF THE TREATMENT-EXPERIENCED PATIENT................ 65
The Treatment-Experienced Patient ......................................................................... 65
Management of Patients with Antiretroviral Treatment Failure...................... 66
Regimen Simplification ................................................................................................... 73
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December 1, 2009

Exposure-Response Relationship and Therapeutic Drug Monitoring
(TDM) for Antiretroviral Agents ........................................................................... 77
Discontinuation or Interruption of Antiretroviral Therapy .................................. 80

CONSIDERATIONS FOR ANTIRETROVIRAL USE IN
SPECIAL PATIENT POPULATIONS ............................................................. 84
Acute HIV Infection .......................................................................................................... 84
HIV-Infected Adolescents .............................................................................................. 87
HIV and Illicit Drug Users (IDUs)................................................................................ 90
HIV-Infected Women ....................................................................................................... 95
Considerations in Managing Patients with HIV-2 Infection ............................. 99

ANTIRETROVIRAL CONSIDERATIONS IN PATIENTS
WITH COINFECTIONS ................................................................................... 102
Hepatitis B (HBV)/HIV Coinfection ............................................................................102
Hepatitis C (HCV)/HIV Coinfection ............................................................................103
Mycobacterium Tuberculosis Disease or Latent Tuberculosis
Infection with HIV Coinfection..............................................................................106

LIMITATIONS TO TREATMENT SAFETY AND EFFICACY ........................... 111
Adherence to Antiretroviral Therapy .........................................................................111
Adverse Effects of Antiretroviral Agents..................................................................114
Drug Interactions...............................................................................................................125

PREVENTING SECONDARY TRANSMISSION OF HIV .................................. 144
Prevention Counseling ...................................................................................................144
Antiretroviral Therapy as Prevention ........................................................................144
Summary ..............................................................................................................................144

CONCLUSION ................................................................................................... 146

TABLES
Table 1. Outline of the Guidelines Development Process ............................ 1
Table 2. Rating Scheme for Recommendations ............................................... 2
Table 3. Laboratory Monitoring Schedule for Patients Prior to and After
Initiation of Antiretroviral Therapy .................................................................. 6
Table 4. Recommendations for Using Drug Resistance Assays ............... 12
Table 5a. Antiretroviral Regimens Recommended for
Treatment-Naïve Patients .................................................................................... 39
Table 5b. Antiretroviral Regimens that May be Acceptable and
Regimens to be Used with Caution ................................................................... 40
Table 6. Advantages and Disadvantages of Antiretroviral Components
Recommended as Initial Antiretroviral Therapy ........................................ 51
Table 7. Antiretroviral Components Not Recommended as
Initial Therapy .......................................................................................................... 54
Table 8. Antiretroviral Regimens or Components That Should Not Be
Offered At Any Time .............................................................................................. 62
Table 9. Suggested Minimum Target Trough Concentrations ....................... 79

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December 1, 2009

Table 10. Identifying, Diagnosing, and Managing Acute
HIV-1 Infection ........................................................................................................... 86
Table 11. Strategies to Improve Adherence to Antiretroviral Therapy .......113
Table 12. Antiretroviral Therapy-Associated Adverse Effects and
Management Recommendations .......................................................................116
Table 13. Drugs That Should Not Be Used With PI, NNRTI, or CCR5
Antagonist Antiretrovirals.......................................................................................129
Table 14a. Drug Interactions Between Protease Inhibitors (PIs) and
Other Drugs.................................................................................................................130
Table 14b. Drug Interactions Between NNRTIs and Other Drugs ...............136
Table 14c. Drug Interactions Between NRTIs and Other Drugs
(including antiretroviral agents) ...........................................................................139
Table 14d. Drug Interactions Between CCR5 Antagonist and
Other Drugs.................................................................................................................140
Table 14e. Drug Interactions Between Integrase Inhibitor and
Other Drugs.................................................................................................................140
Table 15a. Interactions Among Protease Inhibitors ...........................................141
Table 15b. Interactions Between NNRTIs, Maraviroc, Raltegravir,
and PIs ..........................................................................................................................142

APPENDIX A: Financial Disclosure for Members of the DHHS Panel
on Antiretroviral Guidelines for Adults and Adolescents ........................ 147

APPENDIX B: Tables
Appendix Table 1. Characteristics of Nucleoside Reverse
Transcriptase Inhibitors (NRTIs).........................................................................152
Appendix Table 2. Characteristics of Non-Nucleoside Reverse
Transcriptase Inhibitors (NNRTIs) .....................................................................154
Appendix Table 3. Characteristics of Protease Inhibitors (PIs) .....................155
Appendix Table 4. Characteristics of Integrase Inhibitors ...............................158
Appendix Table 5. Characteristics of Fusion Inhibitors.....................................158
Appendix Table 6. Characteristics of CCR5 Antagonists.................................158
Appendix Table 7. Antiretroviral Dosing Recommendations in
Patients with Renal or Hepatic Insufficiency .................................................159

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December 1, 2009

DHHS Panel on Antiretroviral Guidelines for
Adults and Adolescents Panel Roster
These Guidelines were developed by the Department of Health and Human Services (DHHS) Panel on Antiretroviral
Guidelines for Adults and Adolescents (a Working Group of the Office of AIDS Research Advisory Council).

Panel Co-Chairs:
John G. Bartlett, Johns Hopkins University, Baltimore, MD
H. Clifford Lane, National Institutes of Health, Bethesda, MD

Executive Secretary:
Alice K. Pau, National Institutes of Health, Bethesda, MD

Members of the Panel:
Jean Anderson Johns Hopkins University, Baltimore, MD
Judith Currier University of California–Los Angeles, Los Angeles, CA
Eric Daar University of California–Los Angeles, Harbor-UCLA Medical Center, Los Angeles, CA
Paul Dalton San Francisco, CA
Steven G. Deeks University of California–San Francisco, San Francisco, CA
Carlos del Rio Emory University, Atlanta, GA
Robert T. Dodge University of North Carolina, Chapel Hill, NC
Courtney V. Fletcher University of Nebraska Medical Center, Omaha, NE
Gerald Friedland Yale University School of Medicine, New Haven, CT
Joel Gallant Johns Hopkins University, Baltimore, MD
Roy M. Gulick Weill Medical College of Cornell University, New York, NY
W. Keith Henry Hennepin County Medical Center & University of Minnesota, Minneapolis, MN
Martin S. Hirsch Harvard Medical School & Massachusetts General Hospital, Boston, MA
Michael D. Hughes Harvard School of Public Health, Boston, MA
Morris Jackson AIDS Project Los Angeles, Los Angeles, CA
Wilbert Jordan OASIS HIV Clinic & Charles R. Drew University of Medicine & Science, Los Angeles, CA
Daniel R. Kuritzkes Harvard Medical School & Brigham and Women’s Hospital, Boston, MA
Heidi Nass University of Wisconsin, Madison, WI
James Neaton University of Minnesota, Minneapolis, MN
Michael Saag University of Alabama at Birmingham, Birmingham, AL
Paul Sax Harvard Medical School & Brigham and Women’s Hospital, Boston, MA
Renslow Sherer University of Chicago, Chicago, IL
Mark Sulkowski Johns Hopkins University, Baltimore, MD
Nelson Vergel Program for Wellness Restoration, Houston, TX
Paul Volberding University of California–San Francisco & VA Medical Center, San Francisco, CA
David A. Wohl University of North Carolina, Chapel Hill, NC

Participants from the Department of Health and Human Services:
Victoria Cargill National Institutes of Health
Laura Cheever Health Resources and Services Administration
Christopher M. Gordon National Institutes of Health
Jonathan Kaplan Centers for Disease Control and Prevention
Bill Kapogiannis National Institutes of Health
Henry Masur National Institutes of Health
Lynne Mofenson National Institutes of Health
Jeffrey Murray Food and Drug Administration
Kimberly Struble Food and Drug Administration

Non-Voting Observer:
Sarita Boyd National Institutes of Health, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD

Guidelines Acknowledgement List
The Panel would also like to acknowledge the following individuals for their assistance in the preparation of this revision:
Geoff Gottlieb (University of Washington, Seattle, WA), Scott Letendre (University of California–San Diego), Christine Malati
(National Institutes of Health), Stacy Newula (Food and Drug Administration), and Kevin Robertson (University of North
Carolina, Chapel Hill, NC)

Updated December 1, 2009

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December 1, 2009

Introduction (Updated November 3, 2008)
Antiretroviral therapy for treatment of human immunodeficiency virus type 1 (HIV-1) infection has improved steadily
since the advent of potent combination therapy in 1996. New drugs have been approved that offer new mechanisms of
action, improvements in potency and activity even against multi-drug–resistant viruses, dosing convenience, and
tolerability.

The Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and
Adolescents (the Panel) is a working group of the Office of AIDS Research Advisory Council (OARAC). The primary
goal of the Panel is to provide recommendations for HIV care practitioners based on current knowledge of
antiretroviral drugs used to treat adults and adolescents with HIV infection in the United States. The Panel reviews
new evidence and updates recommendations when needed. The primary areas of attention have included baseline
assessment, treatment goals, indications for initiation of antiretroviral therapy, choice of the initial regimen in
treatment-naïve patients, drugs or combinations to be avoided, management of adverse effects and drug interactions,
management of treatment failure, and special considerations in specific patient populations.

These guidelines generally represent the state of knowledge regarding the use of antiretroviral agents. However, as the
science rapidly evolves, the availability of new agents and new clinical data may rapidly change therapeutic options
and preferences. (Information included in these guidelines may not represent FDA approval or approved labeling for
the particular products or indications in question. Specifically, the terms “safe” and “effective” may not be
synonymous with the FDA-defined legal standards for product approval.) The guidelines, therefore, are updated
frequently by the Panel and are available as a “living document” on the AIDSinfo Web site
(http://www.aidsinfo.nih.gov). However, these guidelines cannot always keep pace with the rapid evolution of new
data in this field, and the guidelines cannot provide guidance for all patients. Therefore, clinicians need to exercise
good judgment in management decisions tailored to unique patient circumstances.

GUIDELINES DEVELOPMENT PROCESS

An outline of the composition of the Panel and guidelines process can be found in Table 1.

Table 1. Outline of the Guidelines Development Process (Updated November 3, 2008)
Page 1 of 2
Topic Comment
Goal of the Provide guidance to HIV care practitioners on the optimal use of antiretroviral agents for the
guidelines treatment of HIV infection in adults and adolescents in the United States.
Panel members The Panel is composed of more than 30 voting members who have expertise in HIV care and
research. The U.S. government representatives include at least one representative from each of
the following DHHS agencies: Centers for Disease Control and Prevention (CDC), Food and
Drug Administration (FDA), Health Resource Services Administration (HRSA), and National
Institutes of Health (NIH). These members are appointed by their respective agencies.
Approximately two thirds of the Panel members are nongovernmental scientific members.
There are 4–5 community members. Members who do not represent U.S. government agencies
are selected after an open announcement to call for nominations. Each member serves on the
Panel for a 4-year term, with an option to be reappointed for an additional term. A list of the
current members can be found on Page vi of this document.
Financial All members of the Panel submit a written financial disclosure annually reporting any
disclosure association with manufacturers of antiretroviral drugs or diagnostics used for management of
HIV infections. A list of the latest disclosures can be found in Appendix A of this document.
Users of the
HIV treatment providers
guidelines

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Page 1

Table 1. Outline of the Guidelines Development Process December 1, 2009
Page 2 of 2

Topic Comment
Developer Panel on Antiretroviral Guidelines for Adults and Adolescents—a working group of the
OARAC
Funding source Office of AIDS Research, NIH
Evidence The recommendations generally are based on studies published in peer-reviewed journals. On
collection some occasions, particularly when new information may affect patient safety, unpublished data
presented at major conferences or prepared by the FDA and/or manufacturers as warnings to
the public may be used as evidence to revise the guidelines.
Recommendation
As described in Table 2
grading
Method of Each section of the guidelines is assigned to a working group with expertise in the area of
synthesizing data interest. The members synthesize the available data and propose a recommendation to the
Panel. All proposals are discussed at monthly teleconferences and then are voted on by the
Panel members before being endorsed as official recommendations.
Other guidelines These guidelines focus on treatment for adults and adolescents. Separate guidelines outline the
use of antiretroviral therapy for such populations as pregnant women, children, and those who
experience occupational or non-occupational exposure to HIV. These guidelines are also
available on the AIDSinfo Web site (http://www.aidsinfo.nih.gov). There is a brief
discussion of the management of women of reproductive age and pregnant women in this
document. For a more detailed and up-to-date discussion on this and other special populations,
the Panel defers to the designated expertise offered by panels that have developed those
guidelines.
Update plan The Panel meets monthly by teleconference to review data that may warrant modification of
the guidelines. Updates may be prompted by new drug approvals (or new indications, dosing
formulations, or frequency), new significant safety or efficacy data, or other information that
may have a significant impact on the clinical care of patients. For cases in which significant
new data become available that may affect patient safety, a warning announcement with the
Panel’s recommendations may be made on the AIDSInfo Web site until appropriate changes
can be made in the guidelines document. Updated guidelines are available on the AIDSinfo
Web site (http://www.aidsinfo.nih.gov).
Public comments After release of an update on the AIDSinfo Web site, the public is given a 2-week period to
submit comments to the Panel. These comments are reviewed, and a determination is made as
to whether revisions are indicated. The public is also able to submit comments to the Panel at
any time at contactus@aidsinfo.nih.gov.

Basis for Recommendations

Recommendations in these guidelines are based upon scientific evidence and expert opinion. Each recommended
statement is rated with a letter of A, B, or C that represents the strength of the recommendation and with a numeral I,
II, or III that represents the quality of the evidence (see Table 2 below).

Table 2. Rating Scheme for Recommendations (Updated November 3, 2008)

Strength of Recommendation Quality of Evidence for Recommendation

A: Strong recommendation for the statement I: One or more randomized trials with clinical
B: Moderate recommendation for the statement outcomes and/or validated laboratory endpoints
II: One or more well-designed, nonrandomized trials or
C: Optional recommendation for the statement observational cohort studies with long-term clinical
outcomes
III: Expert opinion


December 1, 2009

HIV Expertise in Clinical Care

Multiple studies have demonstrated that better outcomes are achieved in HIV-infected outpatients cared for by a
clinician with HIV expertise [1-6], which reflects the complexity of HIV infection and its treatment. Thus, appropriate
training and experience, as well as ongoing continuing medical education (CME), are important components for
optimal care. Primary care providers without HIV experience, such as those who provide service in rural or
underserved areas, should identify experts in the region who will provide consultation when needed.

References
1. Kitahata MM, Koepsell TD, Deyo RA, et al. Physicians' experience with the acquired immunodeficiency syndrome
as a factor in patients' survival. N Engl J Med. 1996;334(11):701-706.
2. Kitahata MM, Van Rompaey SE, Shields AW. Physician experience in the care of HIV-infected persons is
associated with earlier adoption of new antiretroviral therapy. J Acquir Immune Defic Syndr. 2000;24(2):106-114.
3. Landon BE, Wilson IB, McInnes K, et al. Physician specialization and the quality of care for human
immunodeficiency virus infection. Arch Intern Med. 2005;165(10):1133-1139.
4. Laine C, Markson LE, McKee LJ, et al. The relationship of clinic experience with advanced HIV and survival of
women with AIDS. AIDS. 1998;12(4):417-424.
5. Kitahata MM, Van Rompaey SE, Dillingham PW, et al. Primary care delivery is associated with greater physician
experience and improved survival among persons with AIDS. J Gen Intern Med. 2003;18(2):95-103.
6. Delgado J, Heath KV, Yip B, et al. Highly active antiretroviral therapy: physician experience and enhanced
adherence to prescription refill. Antivir Ther. 2003;8(5):471-478.


December 1, 2009

Baseline Evaluation (November 3, 2008)
Each HIV-infected patient entering into care should have a complete medical history, physical examination, laboratory
evaluation, and counseling regarding the implications of HIV infection. The purpose is to confirm the presence of HIV
infection, obtain appropriate baseline historical and laboratory data, assure patient understanding about HIV infection,
and initiate care as recommended by the HIV primary care guidelines and by the opportunistic treatment and
prevention guidelines [1-2] . Baseline information then is used to define management goals and plans.

The following laboratory tests should be performed for a new patient during initial patient visits:
• HIV antibody testing (if prior documentation is not available or if HIV RNA is undetectable) (AI);
• CD4 T-cell count (AI);
• Plasma HIV RNA (viral load) (AI);
• Complete blood count, chemistry profile, transaminase levels, BUN and creatinine, urinalysis, screening test
for syphilis (e.g., RPR, VDRL, or treponema EIA), tuberculin skin test (TST) or interferon-γ release assay
(IGRA) (unless there is a history of prior tuberculosis or positive TST or IGRA), anti-Toxoplasma gondii IgG,
hepatitis A, B, and C serologies, and Pap smear in women (AIII);
• Fasting blood glucose and serum lipids if the patient is considered at risk of cardiovascular disease and for
baseline evaluation prior to initiation of combination antiretroviral therapy (AIII); and
• For patients who have pretreatment HIV RNA >1,000 copies/mL, genotypic resistance testing when the patient
enters into care, regardless of whether therapy will be initiated immediately (AIII). For patients who have HIV
RNA levels of 500–1,000 copies/mL, resistance testing also may be considered, even though amplification may
not always be successful (BII). If therapy is deferred, repeat testing at the time of antiretroviral initiation
should be considered (CIII). (See Drug Resistance Testing section.)

In addition:
• Testing for Chlamydia trachomatis and Neisseria gonorrhoeae is encouraged to identify both recent
high-risk sexual behavior and the need for sexually transmitted disease (STD) therapy (BII); and
• Chest x-ray in the presence of pulmonary symptoms or with a positive TST or IGRA test (BIII).
Patients living with HIV infection must often cope with multiple social, psychiatric, and medical issues that are best
addressed through a multidisciplinary approach to the disease. The evaluation also must include assessment of
substance abuse, economic factors (e.g., unstable housing), social support, mental illness, comorbidities, high-risk
behaviors, and other factors that are known to impair the ability to adhere to treatment and to promote HIV
transmission. Once evaluated, these factors should be managed accordingly.
Lastly, education about HIV risk behaviors and effective strategies to prevent HIV transmission to others should be
provided at each patient clinic visit. (See Preventing Secondary Transmission of HIV section.)

References
1. Aberg JA, Kaplan JE, Libman H, et al. Primary care guidelines for the management of persons infected with human
immunodeficiency virus: 2009 update by the HIV medicine Association of the Infectious Diseases Society of
America. Clin Infect Dis. 2009;49(5):651-681.
2. Kaplan JE, Benson C, Holmes KH, et al. Guidelines for prevention and treatment of opportunistic infections in
HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV
Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58(RR-4):1-207.


December 1, 2009

Laboratory Testing for Initial Assessment and
Monitoring While on Antiretroviral Therapy
(Updated December 1, 2009)

A number of laboratory tests are important for initial evaluation of an HIV-1-infected patient upon entry into care,
during follow-up if therapy is not yet initiated, and prior to and after initiation or switch of therapy to assess virologic
and immunologic efficacy of antiretroviral therapy as well as to monitor for laboratory abnormalities that may be
associated with antiretroviral drugs. Table 3 outlines the Panel’s recommendations for the frequency of testing. As
noted in the table, some of the tests may be repeated more frequently if clinically indicated.

Two surrogate markers are used routinely to assess the immune function and level of HIV viremia: CD4 T-cell count
and plasma HIV RNA (viral load). Resistance testing should be used to guide selection of an antiretroviral regimen in
both treatment-naïve and treatment-experienced patients; a viral tropism assay should be performed prior to initiation
of a CCR5 antagonist; and HLA-B*5701 testing should be performed prior to initiation of abacavir. The rationale and
utility of these laboratory tests are discussed below.


December 1, 2009

Table 3. Laboratory Monitoring Schedule for Patients Prior to and After Initiation of
Antiretroviral Therapy (Updated December 1, 2009)
Abbreviations: ABC = abacavir; ART = antiretroviral therapy; EFV = efavirenz; HIVAN = HIV-associated nephropathy; TDF = tenofovir;
ZDV = zidovudine
Entry Follow- ART 2–8 weeks Every 3–6 Every 6 Every 12 Treatment Clinically
into care up before initiation or post-ART months months months failure indicated
ART switch1 initiation or
switch
CD4 T-cell count √ every 3–6 √ √2 √ √
months
HIV RNA √ every 3–6 √ √3 √2 √ √
months
Resistance testing √ √4 √ √

HLA-B*5701 √
testing (if considering
ABC)
Tropism testing √ √ √
(if considering (if
a CCR5 considering a
antagonist) CCR5
antagonist)
Hepatitis B √ √ √ √
serology5 (may repeat if
not immune
and if HBsAg
was (-) at
baseline)
Basic chemistry6 √ every 6– √ √ √ √
12 months
ALT, AST, √ every 6– √ √ √ √
T. bilirubin, 12 months
D. bilirubin

CBC with √ every 3–6 √ √ √ √
differential months (if on ZDV)

Fasting lipid profile √ if normal, √ √ √ √ √
annually (consider (if borderline or (if normal at last
after starting abnormal at last measurement)
new ART) measurement)
Fasting glucose √ if normal, √ √ √ √
annually (if borderline (if normal at last
or abnormal measurement)
at last
measurement)
Urinalysis7 √ √ √ √ √
(patients (if on TDF)
with
HIVAN)
Pregnancy test √ √
(if starting
EFV)

1
Antiretroviral switch may be for treatment failure, adverse effects, or simplification.
2
For adherent patients with suppressed viral load and stable clinical and immunologic status for >2–3 years, some experts may extend the interval for CD4
count and HIV RNA monitoring to every 6 months.
3
If HIV RNA is detectable at 2–8 weeks, repeat every 4–8 weeks until suppression to less than level of detection, then every 3–6 months.
4
For treatment-naïve patients, if resistance testing was performed at entry into care, repeat testing is optional; for patients with viral suppression who are
switching therapy for toxicity or convenience, resistance testing will not be possible and therefore is not necessary.
5
If HBsAg is positive at baseline or prior to initiation of antiretroviral therapy, tenofovir + (emricitabine or lamivudine) should be used as part of
antiretroviral regimen to treat both HBV and HIV infections. If HBsAb is negative at baseline, Hepatitis B vaccine series should be administered.
6
Serum Na, K, HCO3, Cl, BUN, creatinine, glucose (preferably fasting); some experts suggest monitoring phosphorus while on tenofovir; determination of
renal function should include estimation of creatinine clearance using Cockroft and Gault equation or estimation of glomerular filtration rate based on
MDRD equation.
7
For patients with renal disease, consult “Guidelines for the Management of Chronic Kidney Disease in HIV-Infected Patients: Recommendations of the
HIV Medicine Association of the Infectious Diseases Society of America” [1].


December 1, 2009

CD4+ T-CELL COUNT

The CD4+ T-cell count (or CD4 count) serves as the major clinical indicator of immune function in patients who have
HIV infection. It is one of the key factors in deciding whether to initiate antiretroviral therapy and chemoprophylaxis for
opportunistic infections, and is the strongest predictor of subsequent disease progression and survival according to
clinical trials and cohort studies [2-3] . A significant change (2 standard deviations) between two tests is approximately a
30% change in the absolute count or an increase or decrease in CD4 percentage by 3 percentage points.

• Use of CD4 Count for Initial Assessment. The CD4 count is one of the most important factors in the decision to
initiate antiretroviral therapy and/or prophylaxis for opportunistic infections. All patients should have a baseline CD4
count at entry into care (AI). Recommendations for initiation of antiretroviral therapy based on CD4 count are found in
the Initiating Antiretroviral Therapy section of these guidelines.
• Use of CD4 Count for Monitoring Therapeutic Response. An adequate CD4 response for most patients on therapy
is defined as an increase in CD4 count in the range of 50–150 cells/mm3 per year, generally with an accelerated
response in the first 3 months. Subsequent increases in patients with good virologic control show an average increase
of approximately 50–100 cells/mm3 per year for the subsequent years until a steady state level is reached [4]. Some
patients who initiate therapy with a severely depleted CD4 count may have a blunted increase in their count despite
virologic suppression.

Frequency of CD4 Count Monitoring – In general, CD4 counts should be monitored every 3–4 months to (1)
determine when to start antiretroviral therapy in patients not being treated; (2) assess immunologic response to
antiretroviral therapy; and (3) assess the need for initiation or discontinuation of prophylaxis for opportunistic
infections (AI). For those patients who are adherent to therapy with sustained viral suppression and stable clinical
status for more than 2–3 years, the frequency of CD4 count monitoring may be extended to every 6 months (BIII).

Factors that affect absolute CD4 count – The absolute CD4 count is a calculated value based on the total white blood
cell (WBC) count and the percentages of total and CD4+ T lymphocytes. This absolute number may fluctuate among
individuals or may be influenced by factors that may affect the total WBC and lymphocyte percentages, such as use of
bone marrow–suppressive medications or the presence of acute infections. Splenectomy [5-6] or coinfection with
HTLV-1 [7] may cause misleadingly elevated absolute CD4 counts. Alpha-interferon, on the other hand, may reduce
the absolute CD4 number without changing the CD4 percentage [8] . In all these cases, CD4 percentage remains stable
and may be a more appropriate parameter to assess the patient’s immune function.

PLASMA HIV RNA TESTING

Plasma HIV RNA (viral load) should be measured in all patients at baseline and on a regular basis thereafter,
especially in patients who are on treatment, because viral load is the most important indicator of response to
antiretroviral therapy (AI). Analysis of 18 trials that included more than 5,000 participants with viral load monitoring
showed a significant association between a decrease in plasma viremia and improved clinical outcome [9] . Thus, viral
load testing serves as a surrogate marker for treatment response [10] and can be useful in predicting clinical
progression [11-12] . The minimal change in viral load considered to be statistically significant (2 standard deviations)
is a threefold, or a 0.5 log10 copies/mL change. One key goal of therapy is suppression of viral load to below the limits
of detection (below 40–75 copies/mL by most commercially available assays). For most individuals who are adherent
to their antiretroviral regimens and who do not harbor resistance mutations to the prescribed drugs, viral suppression is
generally achieved in 12–24 weeks, even though it may take a longer time in some patients. Recommendations for the
frequency of viral load monitoring are summarized below.

• At Initiation or Change in Therapy. Plasma viral load should be measured before initiation of therapy and
preferably within 2–4 weeks, and not more than 8 weeks, after treatment initiation or after treatment modification
(BI). Repeat viral load measurement should be performed at 4–8-week intervals until the level falls below the assay’s
limit of detection (BII).
• In Patients Who Have Viral Suppression but Therapy Was Modified Due to Drug Toxicity or Regimen
Simplification. Viral load measurement should be performed within 2–8 weeks after changing therapy. The purpose


December 1, 2009

of viral load monitoring at this point is to confirm potency of the new regimen (BII).
• In Patients on a Stable Antiretroviral Regimen. Viral load should be repeated every 3–4 months or as clinically
indicated (BII). In adherent patients who have suppressed viral loads for more than 2–3 years and who are at stable
clinical and immunologic status, some clinicians may extend the interval to every 6 months (BIII).

Monitoring in Patients with Suboptimal Response. In addition to viral load monitoring, a number of additional
factors, such as adherence to prescribed medications, altered pharmacology, or drug interactions, should be assessed.
Patients who fail to achieve viral suppression should undergo resistance testing to aid in the selection of an alternative
regimen, as discussed in the Drug Resistance Testing and Management of the Treatment-Experienced Patient
sections (AI).

References
1. Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney disease in HIV-
infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of
America. Clin Infect Dis. 2005;40(11):1559-1585.
2. Mellors JW, Munoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1
infection. Ann Intern Med. 1997;126(12):946-954.
3. Egger M, May M, Chene G, et al. Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy:
a collaborative analysis of prospective studies. Lancet. 2002;360(9327):119-129.
4. Kaufmann GR, Perrin L, Pantaleo G, et al. CD4 T-lymphocyte recovery in individuals with advanced HIV-1
infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med.
2003;163(18):2187-2195.
5. Zurlo JJ, Wood L, Gaglione MM, et al. Effect of splenectomy on T lymphocyte subsets in patients infected with the
human immunodeficiency virus. Clin Infect Dis. 1995;20(4):768-771.
6. Bernard NF, Chernoff DN, Tsoukas CM. Effect of splenectomy on T-cell subsets and plasma HIV viral titers in
HIV-infected patients. J Hum Virol. 1998;1(5):338-345.
7. Casseb J, Posada-Vergara MP, Montanheiro P, et al. T CD4+ cells count among patients co-infected with human
immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1): high prevalence of
tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). Rev Inst Med Trop Sao Paulo.
2007;49(4):231-233.
8. Berglund O, Engman K, Ehrnst A, et al. Combined treatment of symptomatic human immunodeficiency virus type
1 infection with native interferon-alpha and zidovudine. J Infect Dis. 1991;163(4):710-715.
9. Murray JS, Elashoff MR, Iacono-Connors LC, et al. The use of plasma HIV RNA as a study endpoint in efficacy
trials of antiretroviral drugs. AIDS. 1999;13(7):797-804.
10. Hughes MD, Johnson VA, Hirsch MS, et al. Monitoring plasma HIV-1 RNA levels in addition to CD4+
lymphocyte count improves assessment of antiretroviral therapeutic response. ACTG 241 Protocol Virology
Substudy Team. Ann Intern Med. 1997;126(12):929-938.
11. Marschner IC, Collier AC, Coombs RW, et al. Use of changes in plasma levels of human immunodeficiency virus
type 1 RNA to assess the clinical benefit of antiretroviral therapy. J Infect Dis. 1998;177(1):40-47.
12. Thiébaut R, Morlat P, Jacqmin-Gadda H, et al. Clinical progression of HIV-1 infection according to the viral
response during the first year of antiretroviral treatment. Groupe d'Epidémiologie du SIDA en Aquitaine (GECSA).
AIDS. 2000;14(8):971-978.


December 1, 2009

DRUG RESISTANCE TESTING (Updated December 1, 2009)

Panel’s Recommendations:
• HIV drug resistance testing is recommended for persons with HIV infection when they enter into care
regardless of whether therapy will be initiated immediately or deferred (AIII). If therapy is deferred, repeat
testing at the time of antiretroviral therapy initiation should be considered (CIII). HIV drug resistance testing
should be performed to assist in the selection of active drugs when changing antiretroviral regimens in
patients with virologic failure and HIV RNA levels >1,000 copies/mL (AI). In persons with >500 but <1000
copies/mL, testing may be unsuccessful but should still be considered (BII).
• Drug resistance testing should also be performed when managing suboptimal viral load reduction (AII).
• Drug resistance testing in the setting of virologic failure should be performed while the patient is taking
prescribed antiretroviral drugs, or, if not possible, within 4 weeks after discontinuing therapy (AII).
• Genotypic resistance testing is recommended for all pregnant women prior to initiation of therapy (AIII) and
for those entering pregnancy with detectable HIV RNA levels while on therapy (AI).
• Genotypic testing is recommended as the preferred resistance testing to guide therapy in antiretroviral naïve
patients and in patients with suboptimal virologic responses or virologic failure while on first or second
regimens (AIII).
• Addition of phenotypic testing to genotypic testing is generally preferred for persons with known or suspected
complex drug resistance mutation patterns, particularly to protease inhibitors (BIII).

Genotypic and Phenotypic Resistance Assays
Genotypic and phenotypic resistance assays are used to assess viral strains and inform selection of treatment
strategies. Standard assays provide information on resistance to nucleoside and non-nucleoside reverse transcriptase
and protease inhibitors. Testing to evaluate integrase and fusion inhibitor resistance can also be performed through
some commercial laboratories. No commercial assays are currently available for assessing resistance to CCR5
antagonists.

Genotypic Assays

Genotypic assays detect drug resistance mutations present in relevant viral genes. Most genotypic assays involve
sequencing of the reverse transcriptase and protease genes to detect mutations that are known to confer drug
resistance. A genotypic assay that assesses mutations in the integrase gene is also commercially available. Genotypic
assays can be performed rapidly with results available within 1–2 weeks of sample collection. Interpretation of test
results requires knowledge of the mutations that different antiretroviral drugs select for and of the potential for cross
resistance to other drugs conferred by certain mutations. The International AIDS Society-USA (IAS-USA) maintains a
list of updated significant resistance-associated mutations in the reverse transcriptase, protease, integrase, and
envelope genes (see http://www.iasusa.org/resistance_mutations) [1] . The Stanford University HIV Drug
Resistance Database (http://hivdb.stanford.edu) also provides helpful guidance for interpreting genotypic resistance
test results. Various techniques are now available to assist the provider in interpreting genotypic test results [2-5] .
Clinical trials have demonstrated the benefit of consultation with specialists in HIV drug resistance in improving
virologic outcomes [6] . Clinicians are thus encouraged to consult a specialist to facilitate interpretation of genotypic
test results and the design of an optimal new regimen.

Phenotypic Assays

Phenotypic assays measure the ability of a virus to grow in different concentrations of antiretroviral drugs. Reverse
transcriptase and protease gene sequences and, more recently, integrase and envelope sequences derived from patient
plasma HIV RNA are inserted into the backbone of a laboratory clone of HIV or used to generate pseudotyped viruses
that express the patient-derived HIV genes of interest. Replication of these viruses at different drug concentrations is
monitored by expression of a reporter gene and is compared with replication of a reference HIV strain. The drug
concentration that inhibits 50% of viral replication (i.e., the median inhibitory concentration [IC]50) is calculated, and
the ratio of the IC50 of test and reference viruses is reported as the fold increase in IC50 (i.e., fold resistance).


December 1, 2009

Automated phenotypic assays are commercially available with results reported in 2–3 weeks. However, phenotypic
assays cost more to perform than genotypic assays. In addition, interpretation of phenotypic assay results is
complicated by incomplete information regarding the specific resistance level (i.e., fold increase in IC50) that is
associated with drug failure, although clinically significant fold increase cutoffs are now available for some drugs [7-
11] . Again, consultation with a specialist can be helpful for interpreting test results.

Further limitations of both genotypic and phenotypic assays include lack of uniform quality assurance for all available
assays, relatively high cost, and insensitivity for minor viral species. Despite being present, drug-resistant viruses
constituting less than 10%–20% of the circulating virus population will probably not be detected by available assays.
This limitation is important because after drugs exerting selective pressure on drug-resistant populations are
discontinued, a wild-type virus often re-emerges as the predominant population in the plasma. This results in a
decrease of the proportion of virus with resistance mutations to below the 10%–20% threshold [12-14] . For some
drugs, this reversion to predominantly wild-type virus can occur in the first 4–6 weeks after drugs are stopped.
Prospective clinical studies have shown that, despite this plasma reversion, reinstitution of the same antiretroviral
agents (or those sharing similar resistance pathways) is usually associated with early drug failure, and the virus present
at failure is derived from previously archived resistant virus [15] . Therefore, resistance testing is of greatest value
when performed before or within 4 weeks after drugs are discontinued (AII). Because detectable resistant virus may
persist in the plasma of some patients for longer periods of time, resistance testing beyond 4 to 6 weeks after
discontinuation may still reveal mutations. However, the absence of detectable resistance in such patients must be
interpreted with caution in designing subsequent antiretroviral regimens.

Use of Resistance Assays in Clinical Practice (Table 4)

No definitive prospective data exist to support using one type of resistance assay over another (i.e., genotypic vs.
phenotypic) in different clinical situations. In most situations genotypic testing is preferred because of the faster
turnaround time, lower cost, and enhanced sensitivity for detecting mixtures of wild-type and resistant virus. However,
for patients with a complex treatment history, results derived from both assays might provide critical and
complementary information to guide regimen changes.

Use of Resistance Assays in Determining Initial Treatment

Transmission of drug-resistant HIV strains is well documented and associated with suboptimal virologic response to
initial antiretroviral therapy [16-19]. The likelihood that a patient will acquire drug-resistant virus is related to the
prevalence of drug resistance in persons engaging in high-risk behaviors in the community. In the United States and
Europe, recent studies suggest the risk that transmitted virus will be resistant to at least one antiretroviral drug is in the
range of 6%–16% [20-25], with 3%–5% of transmitted viruses exhibiting resistance to drugs from more than one class
[24, 26] . If the decision is made to initiate therapy in a person with acute HIV infection, resistance testing at baseline
will provide guidance in selecting a regimen to optimize virologic response. Therefore, resistance testing in this
situation is recommended (AIII) using a genotypic assay. In the absence of therapy, resistant viruses may decline over
time to less than the detection limit of standard resistance tests but may still increase the risk of treatment failure when
therapy is eventually initiated. Therefore, if the decision is made to defer therapy, resistance testing during acute HIV
infection should still be performed (AIII). In this situation, the genotypic resistance test result might be kept on record
for several years before it becomes clinically useful. Because it is possible for a patient to acquire drug-resistant virus
(i.e., superinfection) between entry into care and initiation of antiretroviral therapy, repeat resistance testing at the time
treatment is started should be considered (CIII).

Performing drug resistance testing before initiation of antiretroviral therapy in patients with chronic HIV infection is
less straightforward. The rate at which transmitted resistance-associated mutations revert to wild-type virus has not
been completely delineated, but mutations present at the time of HIV transmission are more stable than those selected
under drug pressure, and it is often possible to detect resistance-associated mutations in viruses that were transmitted
several years earlier [27-29]. No prospective trial has addressed whether drug resistance testing prior to initiation of
therapy confers benefit in this population. However, data from several, but not all, studies suggest suboptimal
virologic responses in persons with baseline mutations [16-19, 30-32]. In addition, a cost-effectiveness analysis of
early genotypic resistance testing suggests that baseline testing in this population should be performed [33] . Therefore,
resistance testing in chronically infected persons at the time of entry into HIV care is recommended (AIII). Genotypic


December 1, 2009

testing is generally preferred in this situation because of lower cost, more rapid turnaround time, ability to detect
mixtures of wild-type and resistant virus, and the relative ease of interpretation (AIII). If therapy is deferred, repeat
testing just prior to initiation of antiretroviral therapy should be considered because the patient may have possibly
acquired drug-resistant virus (i.e., superinfection) (CIII).

Presently, drug resistance testing in antiretroviral-naïve persons involves genotypic testing for mutations in the reverse
transcriptase and protease genes. As the use of integrase inhibitors increases, it is possible that genotypic testing for
resistance to this class of drugs will become clinically useful when an integrase inhibitor is being considered as part of
an initial regimen.

Use of Resistance Assays in the Event of Virologic Failure

Resistance assays are useful in guiding decisions for patients experiencing virologic failure while on antiretroviral
therapy. Several prospective studies assessed the utility of resistance testing in guiding antiretroviral drug selection in
patients with virologic failure. These studies involved genotypic assays, phenotypic assays, or both [6, 34-40] . In
general, these studies found that early virologic response to salvage regimens was improved when results of resistance
testing were available to guide changes in therapy, compared with responses observed when changes in therapy were
guided only by clinical judgment. Additionally, one observational study demonstrated improved survival in patients
with detectable HIV plasma RNA when drug resistance testing was performed [41] . Thus, resistance testing appears to
be a useful tool in selecting active drugs when changing antiretroviral regimens for virologic failure in persons with
HIV RNA >1,000 copies/mL (AI). (See Management of the Treatment-Experienced Patient.) In persons with >500
but <1,000 copies/mL, testing may be unsuccessful but should still be considered (BII).

Resistance testing also can help guide treatment decisions for patients with suboptimal viral load reduction (AII).
Virologic failure in the setting of combination antiretroviral therapy is, for certain patients, associated with resistance
to only one component of the regimen [42-44]. In that situation, substituting individual drugs in a failing regimen
might be possible, although this concept will require clinical validation. (See Management of the Treatment-
Experienced Patient.)

Genotypic testing is generally preferred for virologic failure or suboptimal viral load reduction in persons failing their
first or second antiretroviral drug regimen because of lower cost, faster turnaround time, and greater sensitivity for
detecting mixtures of wild-type and resistant virus (AIII). Addition of phenotypic testing to genotypic testing, is
generally preferred for persons with known or suspected complex drug resistance mutation patterns, particularly to
protease inhibitors (BIII).

The clinical utility of resistance testing for integrase and fusion inhibitor resistance is limited at present because of
lack of availability of second-line drugs within these classes; that is, there is no need to test for cross resistance to
other drugs. However, in patients failing integrase- or fusion inhibitor-based regimens, testing for integrase or fusion
inhibitor resistance may be helpful to determine whether to include drugs from these classes in subsequent regimens
(CIII). A coreceptor tropism assay should be performed whenever the use of a CCR5 antagonist is being considered
(AII). (See section on Coreceptor Tropism Assays.)

Use of Resistance Assays in Pregnant Patients

In pregnant women, the goal of antiretroviral therapy is to maximally reduce plasma HIV RNA to provide appropriate
maternal therapy and prevent mother-to-child transmission of HIV. Genotypic resistance testing is recommended for
all pregnant women prior to initiation of therapy (AIII) and for those entering pregnancy with detectable HIV RNA
levels while on therapy (AII). Phenotypic testing may provide additional information in those found to have complex
drug resistance mutation patterns, particularly to protease inhibitors (BIII). Optimal prevention of perinatal
transmission may require initiation of antiretroviral therapy while results of resistance testing are pending. Once the
results are available, the antiretroviral regimen can be changed as needed.


December 1, 2009

Table 4. Recommendations for Using Drug Resistance Assays (Updated December 1, 2009)
Page 1 of 2

Clinical Setting/Recommendation Rationale
Drug resistance assay recommended
In acute HIV infection: Drug resistance testing If treatment is to be initiated immediately, drug
is recommended regardless of whether treatment resistance testing will determine whether drug-resistant
is initiated immediately or deferred (AIII). A virus was transmitted. Test results will help in the
genotypic assay is generally preferred (AIII). design of initial regimens or, if therapy was initiated
prior to results, change regimens.

Genotypic testing is preferable to phenotypic testing
because of lower cost, faster turnaround time, and
greater sensitivity for detecting mixtures of wild-type
and resistant virus.

If treatment is deferred, repeat resistance testing If treatment is deferred, testing should still be performed
should be considered at the time antiretroviral because of the greater likelihood that transmitted
therapy is initiated (CIII). A genotypic assay is resistance-associated mutations will be detected earlier in
generally preferred (AIII). the course of HIV infection. Results of resistance testing
may be important when treatment is initiated. Repeat
testing at the time antiretroviral therapy is initiated should
be considered because the patient may have acquired a
drug-resistant virus (i.e., superinfection).
In treatment-naïve patients with chronic HIV Transmitted HIV with baseline resistance to at least one
infection: Drug resistance testing is drug is seen in 6%–16% of patients, and suboptimal
recommended at the time of entry into HIV care, virologic responses may be seen in patients with
regardless of whether therapy is initiated baseline resistant mutations. Some drug resistance
immediately or deferred (AIII). A genotypic mutations can remain detectable for years in untreated
assay is generally preferred (AIII). chronically infected patients.

If therapy is deferred, repeat resistance testing Repeat testing prior to initiation of antiretroviral therapy
should be considered at the time antiretroviral should be considered because the patient may have
therapy is initiated (CIII). A genotypic assay is acquired a drug-resistant virus (i.e., a superinfection).
generally preferred (AIII).
Genotypic testing is preferred for the reasons noted
previously.
In patients with virologic failure: Drug resistance Testing can help determine the role of resistance
testing is recommended in persons on combination in drug failure and maximize the clinician’s
antiretroviral therapy with HIV RNA levels >1,000 ability to select active drugs for the new regimen.
copies/mL (AI). In persons with HIV RNA levels Drug resistance testing should be performed
>500 but <1,000 copies/mL, testing may be while the patient is taking prescribed
unsuccessful but should still be considered (BII). antiretroviral drugs or, if not possible, within 4
weeks after discontinuing therapy.

A genotypic assay is generally preferred in those Genotypic testing is generally preferred for the
experiencing virologic failure on their first or second reasons noted previously.
regimens (AIII).

Addition of phenotypic assay to genotypic assay is Phenotypic testing can provide useful additional
generally preferred for those with known or suspected information for those with complex drug
complex drug resistance patterns, particularly to resistance mutation patterns, particularly to
protease inhibitors (BIII). protease inhibitors.


Table 4. Recommendations for Using Drug Resistance Assays Therapy December 1, 2009
Page 2 of 2

Clinical Setting/Recommendation Rationale
Drug resistance assay recommended (continued)
In patients with suboptimal suppression of viral load: Testing can help determine the role of resistance and thus
Drug resistance testing is recommended in persons with assist in identifying the number of active drugs available
suboptimal suppression of viral load after initiation of for a new regimen.
antiretroviral therapy (AII).
In HIV-infected pregnant women: Genotypic resistance The goal of antiretroviral therapy in HIV-infected
testing is recommended for all pregnant women prior to pregnant women is to achieve maximal viral suppression
initiation of antiretroviral therapy (AIII) and for those for treatment of maternal HIV infection and for prevention
entering pregnancy with detectable HIV RNA levels of perinatal HIV transmission. Genotypic resistance
while on therapy (AI). testing will assist the clinician in selecting the optimal
regimen for the patient.
Drug resistance assay not usually recommended
After therapy discontinued: Drug resistance testing is Drug resistance mutations might become minor species in
not usually recommended after discontinuation (>4 the absence of selective drug pressure, and available
weeks) of antiretroviral drugs (BIII). assays might not detect minor drug-resistant species. If
testing is performed in this setting, the detection of drug
resistance may be of value; however, the absence of
resistance does not rule out the presence of minor drug-
resistant species.
In patients with low HIV RNA levels: Drug resistance Resistance assays cannot be consistently performed given
testing is not usually recommended in persons with a low HIV RNA levels.
plasma viral load <500 copies/mL (AIII).

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HLA-B*5701 SCREENING (Updated December 1, 2007)

Panel’s Recommendations:
• The Panel recommends screening for HLA-B*5701 before starting patients on an abacavir-containing
regimen, to reduce the risk of hypersensitivity reaction (AI).
• HLA-B*5701-positive patients should not be prescribed abacavir (AI).
• The positive status should be recorded as an abacavir allergy in the patient’s medical record (AII).
• When HLA-B*5701 screening is not readily available, it remains reasonable to initiate abacavir with
appropriate clinical counseling and monitoring for any signs of hypersensitivity reaction (CIII).

The abacavir hypersensitivity reaction (ABC HSR) is a multiorgan clinical syndrome typically seen within the initial 6
weeks of abacavir treatment. This reaction has been reported in 5%–8% of patients participating in clinical trials when
using clinical criteria for the diagnosis, and it is the major reason for early discontinuation of abacavir. (See Table 12.)
Discontinuing abacavir usually promptly reverses HSR, whereas subsequent rechallenge can cause a rapid, severe, and
even life-threatening recurrence.

Studies that evaluated demographic risk factors for ABC HSR have shown racial background as a risk factor, with white
patients generally having a higher risk (5%–8%) than black patients (2%–3%). Several groups reported a highly
significant association between ABC HSR and the presence of the MHC class I allele HLA-B*5701 [1, 2] . An abacavir
skin patch test (ABC SPT) was developed as a research tool to immunologically confirm ABC HSR, because the clinical
criteria used for ABC HSR are overly sensitive and may lead to false-positive ABC HSR diagnoses [3] . A positive ABC
SPT is an abacavir-specific delayed hypersensitivity reaction that results in redness and swelling at the skin site of
application. All ABC SPT–positive patients studied were also positive for the HLA-B*5701 allele [4] . The ABC SPT
could be falsely negative for some patients with ABC HSR. It is not recommended to be used as a clinical tool at this
point. The PREDICT-1 study randomized patients before starting abacavir either to be prospectively screened for HLA-
B*5701 (in which HLA-B*5701–positive patients were not offered abacavir) or to standard of care at the time of the
study (i.e., no screening, with all patients receiving abacavir) [5] . The overall HLA-B*5701 prevalence in this
predominately white population was 5.6%. In this cohort, screening for HLA-B*5701 eliminated immunologic ABC HSR
(defined as ABC SPT positive) compared with standard of care (0% vs. 2.7%), yielding a 100% negative predictive value
with respect to SPT as well as significantly decreasing the rate of clinically suspected ABC HSR (3.4% vs. 7.8%). The


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